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Central Nervous System Cryptococcosis: Parenchymal Calcification
and Large Gelatinous Pseudocysts
Karen S. Caldemeyer, Vincent P. Mathews, Mary K. Edwards-Brown, and Richard R. Smith
Summary: In an 11-year-old immunocompetent girl with protracted cryptococcal infection of the central nervous system, CT
showed multiple areas of parenchymal calcification. MR imaging
showed large gelatinous pseudocysts around the brain stem.
These imaging features and the child’s age are unusual for intracranial cryptococcosis.
with back pain, lethargy, a 2.3-kg weight loss, and vomiting. CSF culture showed 65 leukocytes (1% polymorphonuclear, 88% lymphocytes, 11% monocytes), a glucose
level of 89 mg/dL, and a protein level of 4100 mg/dL. CSF
was negative for cryptococcal antigen, and cytologic findings were normal. Serologic tests for cryptococcosis, histoplasmosis, blastomycetes, coccidioidomycosis, brucella, and syphilis were negative. Urine was negative for
histoplasmosis antigen. CT scans showed multiple areas
of parenchymal calcification and low attenuation in the
posterior fossa. MR images of the brain showed leptomeningeal enhancement; multiple enhancing lesions in the
cortex, basal ganglia, and thalami; dilatation of VirchowRobin spaces; and large cysts compressing the brain stem
(Fig 1). Spinal MR images showed diffuse leptomeningeal
enhancement.
The child underwent a suboccipital craniectomy and
fenestration of the infratentorial cysts. At surgery, a grayish mucoid material was seen throughout the posterior
fossa. CSF obtained at the time of surgery showed an
extremely elevated cryptococcal antigen titer of 1:2560.
The child was subsequently treated with intravenous amphotericin B.
Index term: Brain, infection
Cryptococcosis, the most common mycotic
infection of the central nervous system (CNS),
primarily manifests as meningitis (1–7). Several
reports have described extension of the meningeal infection along perivascular spaces giving
rise to small cysts, termed gelatinous pseudocysts, in the Virchow-Robin spaces and adjacent brain (1– 8). We present a case of CNS
cryptococcosis in which there were large
gelantinous pseudocysts compressing the brain
stem and multiple areas of intraparenchymal
calcification.
Case Report
Discussion
In September 1993, a then 9-year-old girl was treated at
another hospital for headache, nausea, vomiting, neck and
back pain, and left-sided numbness. The child was afebrile
and confused and had nuchal rigidity. There was no papilledema or focal neurologic deficit. Lumbar puncture disclosed three leukocytes, a protein level of 120 mg/dL, and
a glucose level of 91 mg/dL. Cerebrospinal fluid (CSF)
gram stain and bacterial, fungal, acid fast bacillus, and
viral cultures were negative. Computed tomography (CT)
and magnetic resonance (MR) imaging showed mild ventricular dilatation. The child was placed on amoxicillin and
symptoms improved. Three weeks later, the girl was seen
for a left-sided focal seizure and placed on anticonvulsant
medication. Two months later, MR imaging showed an
increase in ventricular size, and a ventriculoperitoneal
shunt was placed. CSF culture was again noncontributory.
The child was referred to our institution in July 1995
Cryptococcosis, caused by an encapsulated
yeastlike fungus, is the most common CNS mycotic infection (1– 4). Cryptococcus neoformans
is a ubiquitous organism found in mammal and
bird feces, particularly pigeon droppings (2, 3,
5, 7). CNS cryptococcosis is believed to result
from hematogenous dissemination from the
lung (1–3, 5, 6). Although the infection may
occur in immunocompetent persons, many patients have an underlying chronic illness, such
as diabetes mellitus, collagen vascular disease,
chronic renal disease, alcoholism, or malignantneoplasms, particularly lymphoreticular
disor-ders, or they are on immunosuppressive
medication (2– 6). Patients with acquired im-
Received November 14, 1995; accepted after revision March 17, 1996.
From the Department of Radiology, Indiana University School of Medicine, University Hospital, Room 0279, 550 N University Blvd, Indianapolis, IN
46202. Address reprint requests to Karen S. Caldemeyer, MD.
AJNR 18:107–109, Jan 1997 0195-6108/97/1801–0107
© American Society of Neuroradiology
107
108
CALDEMEYER
AJNR: 18, January 1997
Fig 1. MR findings in an 11-year-old
girl with protracted cryptococcal infection
of the CNS.
A and B, Precontrast T1-weighted
(800/20 [repetition time/echo time]) (A)
and T2-weighted (2500/80) (B) images
show multiple posterior fossa extraaxial
cysts compressing the adjacent brain
stem.
C and D, Contrast-enhanced T1weighted (800/20) images show diffuse
enhancement of the leptomeninges and
along the margins of the posterior fossa
cysts. At surgery, these cysts were seen to
be filled with grayish mucoid material.
muno-deficiency syndrome (AIDS) are particularly susceptible to intracranial cryptococcosis
(1, 3). Cryptococcosis may occur at any age,
but is rare before puberty (3).
Encapsulation occurs in response to the
host’s immunologic attack on the organism (1,
3). The capsule consists of viscous acidic polysaccharides, which may produce mucoid deposits in the brain and subarachnoid space (1,
3, 5).
CNS cryptococcosis commonly presents with
nonspecific manifestations of meningitis and
encephalitis, such as headache, mental aberrations, low-grade fever, meningismus, and evidence of increased intracranial pressure (2, 3,
5). The course may be fulminant or chronic and
insidious depending on the host’s resistance
and the inoculum of infection (1, 3, 6). CSF
pressure is often increased, and there may be
mild to moderate leukocytosis and decreased
glucose and elevated protein levels (2, 3, 5).
Infected patients may have elevated cryptococcal antigen titers in the serum or CSF (3, 6). The
level of antigen titer corresponds to the severity
of disease (5). Organisms may be detected by
microscopic examination and culture (3, 6).
CNS cryptococcosis primarily manifests as
meningitis, most pronounced at the base of the
brain (1–3, 6, 7). The infection often provokes
little inflammatory reaction, owing to the host’s
immunity and to the immunosuppressive effect
of the organism’s capsule (1– 4, 7). A grayish,
mucinous exudate accumulates over the brain
surface (3, 7). Infection of the meninges may
AJNR: 18, January 1997
spread to the adjacent brain through the subarachnoid space or along the ependymal surface (2, 3). As the infection spreads along the
Virchow-Robin spaces that accompany perforating arteries, the perivascular spaces may become distended with mucoid, gelatinous material that originates from the organism’s capsule
(2, 4, 5, 7). Larger collections of organisms and
gelatinous capsular material have been termed
gelatinous pseudocysts (1, 7). Mass lesions
representing cryptococcomas may occur, particularly in the deep gray matter (1, 6).
Imaging findings are primarily manifestations
of meningitis. Hydrocephalus often develops as
a result of meningeal scarring (2, 6). Punctate
hyperintensities, representing dilated perivascular spaces or cryptococcomas, are frequently
seen in the basal ganglia, thalami, and midbrain
on T2-weighted MR images (1, 7). Proliferating
masses of organisms and gelatinous material
may distend the subarachnoid spaces (2, 8).
Granulomas may be seen throughout the brain,
along the ependyma, in the choroid plexus, and
along the spinal cord and spinal nerve roots (2,
5–7). Contrast enhancement of the meninges
and cryptococcomas may or may not occur and
frequently is absent in AIDS-related cryptococcosis (1, 6). Calcification of cryptococcomas is
rare (2).
Our patient showed findings of chronic cryptococcal meningitis. While leptomeningeal and
miliary nodular enhancement have been described (7), we have not found reports of the
very large gelatinous pseudocysts seen in this
patient. These mucinous collections are typi-
CRYPTOCOCCOSIS
109
cally small and found along the meninges, in the
perivascular spaces, and in the deep gray structures (2, 8). Larger cysts may arise from coalescence of smaller lesions and are seen predominantly in the basal ganglia and thalami (8).
These cystic lesions are less common than in
the past owing to earlier diagnosis and treatment of CNS cryptococcosis (2). Our patient
had a long, untreated course, which most likely
contributed to this flagrant manifestation. She
also had parenchymal calcification, a rare finding in CNS cryptococcosis. This again most
likely occurred as a result of the protracted disease course.
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